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Search     Simple Advanced Related Clinical Trials from ClinicalTrials.gov  Search the ESRNexus medical and societal libraries for all of the following terms: Show articles that do not have abstracts  Searching for related clinical trials... Results(1-25 of 25,000) Sort By: Publication Date Relevance Took: 4.869 seconds to search 17,750,454 articles.  Action: Copy Results to new Clipboard Build Search Link Page 1 of 1000 1 2 3 4 > Last >> (25000 articles found) Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus 2006 Siebenhofer, A., Plank, J., Berghold, A., Jeitler, K., Horvath, K., Narath, M., Gfrerer, R., and Pieber, T. R. BACKGROUND: Short acting insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. OBJECTIVES: To assess the effects of short acting insulin analogues versus regular human insulin. SEARCH STRATEGY: The Cochrane Library (Issue 3, 2005), MEDLINE, EMBA... ( view more )SE until September 2005. SELECTION CRITERIA: Randomised controlled trials with an intervention duration of at least 4 weeks. DATA COLLECTION AND ANALYSIS: Trial selection and evaluation of study quality was done independently by two reviewers. MAIN RESULTS: Altogether 8274 participants took part in 49 randomised controlled studies. Most studies were of poor methodological quality.In patients with type 1 diabetes, the weighted mean difference (WMD) of HbA1c was -0.1% (95% CI: -0.2 to -0.1) in favour of insulin analogue, whereas in patients with type 2 diabetes the WMD was 0.0% (95% CI: -0.1 to 0.0).In subgroup analyses of different types of interventions in type 1 diabetic patients, the WMD in HbA1c was -0.2% (95% CI: -0.3 to -0.1) in favour of insulin analogue in studies using continuous subcutaneous insulin injections (CSII), whereas for conventional intensified insulin therapy (IIT) studies the WMD in HbA1c was -0.1% (95% CI: -0.1 to 0.0).The WMD of the overall mean hypoglycaemic episodes per patient per month was -0.2 (95% CI: -1.1 to 0.7) and -0.2 (95% CI: -0.5 to 0.1) for analogues in comparison to regular insulin in patients with type 1 diabetes and type 2 diabetes, respectively.For studies in type 1 diabetes patients the incidence of severe hypoglycaemia ranged from 0 to 247.3 (median 21.8) episodes per 100 person-years for insulin analogues and from 0 to 544 (median 46.1) for regular insulin, in type 2 the incidence ranged from 0 to 30.3 (median 0.3) episodes per 100 person-years for insulin analogues and from 0 to 50.4 (median 1.4) for regular insulin.No study was designed to investigate possible long term effects (e.g. mortality, diabetic complications), in particular in patients with diabetes related complications. AUTHORS' CONCLUSIONS: Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. For safety purposes, we need a long-term follow-up of large numbers of patients and well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child. PLAIN LANGUAGE SUMMARY: Short acting insulin analogues in diabetes mellitusShort acting insulin analogues (Lispro, Aspart, Glulisine) act more quickly than regular human insulin. It can be injected immediately before meals and leads to lower blood sugar levels after food intake. Our analysis showed that short acting insulin analogues were almost identically effective to regular human insulin in long term glycaemic control and were associated with similar episodes of low blood sugar (hypoglycaemia). No information on late complications such as problems with the eyes, kidneys or feet are existing. Until long term safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues ( view less ) View Full Abstract View Article Details   Related Articles Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study 2002 Festa, A., D'Agostino, R. J., Tracy, R. P., Haffner, S. M., and Insulin, ResistanceAtherosclerosisStudy Elevated serum levels of acute-phase proteins, indicating chronic subclinical inflammation, have been associated with cardiovascular disease as well as the insulin resistance syndrome. Chronic inflammation may also be a risk factor for developing type 2 diabetes. We studied the concentrations of C-... ( view more )reactive protein (CRP), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) in 1,047 nondiabetic subjects in relation to incident diabetes within 5 years in the Insulin Resistance Atherosclerosis Study. Subjects with diabetes at follow-up (n = 144) had higher baseline levels of fibrinogen (mean +/- SD; 287.8 +/- 58.8 vs. 275.1 +/- 56.0 mg/dl; P = 0.013) as well as of CRP (median [interquartile range]; 2.40 [1.29, 5.87] vs. 1.67 mg/l [0.75, 3.41]; P = 0.0001) and PAI-1 (24 [15, 37.5] vs. 16 ng/ml [9, 27]; P = 0.0001) than nonconverters. The odds ratio (OR) of converting to diabetes was significantly increased with increasing baseline concentrations of the inflammatory markers. In contrast to PAI-1, the association of CRP and fibrinogen with incident diabetes was significantly attenuated after adjustment for body fat (BMI or waist circumference) or insulin sensitivity (S(I)), as assessed by a frequently sampled intravenous glucose tolerance test. In a logistic regression model that included age, sex, ethnicity, clinical center, smoking, BMI, S(I), physical activity, and family history of diabetes, PAI-1 still remained significantly related to incident type 2 diabetes (OR [95% CI] for 1 SD increase: 1.61 [1.20-2.16]; P = 0.002). Chronic inflammation emerges as a new risk factor for the development of type 2 diabetes; PAI-1 predicts type 2 diabetes independent of insulin resistance and other known risk factors for diabetes ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Elevations in markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study 2004 Hanley, A. J., Williams, K., Festa, A., Wagenknecht, L. E., D'Agostino, R. B. J., Kempf, J., Zinman, B., Haffner, S. M., and insulin, resistanceatherosclerosisstudy A limited number of studies have reported associations of markers of liver injury, including elevated concentrations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), with prospective risk of type 2 diabetes. However, only one study has adjusted for a detailed measure of insul... ( view more )in sensitivity (insulin sensitivity index [S(i)]), which is important given associations of obesity and S(i) with nonalcoholic fatty liver disease (NAFLD). Our objective was to investigate the associations of elevated AST and ALT with incident type 2 diabetes among 906 participants in the Insulin Resistance Atherosclerosis Study who were nondiabetic at baseline. S(i) and acute insulin response (AIR) were measured directly from the frequently sampled intravenous glucose tolerance test among black, Hispanic, and non-Hispanic white participants aged 40-69 years. After 5.2 years, 148 individuals had developed type 2 diabetes. Baseline AST and ALT were positively correlated with fasting insulin (r = 0.22 and r = 0.35, respectively), waist circumference (r = 0.18 and r = 0.34), and fasting glucose (r = 0.13 and r = 0.29) and inversely with S(i) (r = -0.18 and r = -0.30; all P < 0.0001). In separate logistic regression models adjusting for age, sex, ethnicity, clinical center, and alcohol consumption, participants in the highest quartiles (Q4) of AST and ALT were at significantly increased risk of incident type 2 diabetes compared with those in the lowest three quartiles (Q1-Q3): AST: odds ratio (OR) 1.73 (95% CI 1.17-2.57); ALT: OR 2.32 (1.36-3.75). After further adjustment for smoking, waist circumference, triglyceride, HDL, impaired glucose tolerance, S(i), and AIR, both AST and ALT remained significantly associated with incident type 2 diabetes: AST, Q4 vs. Q1-Q3: OR 1.98 (1.23-3.17); ALT, Q4 vs. Q1-Q3: OR 2.00 (1.22-3.28). There were no interactions of sex, ethnicity, obesity, impaired glucose tolerance, or S(i) with AST or ALT in the prediction of type 2 diabetes. When entered into the same model with adjustment for demographic variables, both C-reactive protein and ALT independently predicted type 2 diabetes. In addition, AST and ALT were positively associated with incident type 2 diabetes after excluding former and moderate to heavy drinkers. In conclusion, AST and ALT independently predict type 2 diabetes. Baseline elevations of these markers may reflect NAFLD or related pathologies ( view less ) View Full Abstract View Article Details   Related Articles Cardiovascular disease risk factors predict the development of type 2 diabetes: the insulin resistance atherosclerosis study 2004 D'Agostino, R. B. J., Hamman, R. F., Karter, A. J., Mykkanen, L., Wagenknecht, L. E., Haffner, S. M., and Insulin, ResistanceAtherosclerosisStudyInvestigators OBJECTIVE: In a few previous studies, cardiovascular disease (CVD) risk factors (RFs) have been shown to predict diabetes. Our objective was to determine whether the presence of CVD RFs predict the eventual development of diabetes after controlling for known RFs, such as directly measured insulin r... ( view more )esistance and obesity. RESEARCH DESIGN AND METHODS: We studied 872 participants with normal or impaired glucose tolerance (IGT) who were enrolled at baseline in the Insulin Resistance Atherosclerosis Study (IRAS). Of these, 143 (16%) developed type 2 diabetes in 5 years. Using these participants, a series of logistic regression models were fit to address the question. RESULTS: Significant RFs for developing type 2 diabetes included high plasminogen activator inhibitor-1, hypertension, high triglycerides, low levels of HDL cholesterol, and IGT. The 5-year cumulative incidence of type 2 diabetes by the number of RFs (0-5) was as follows: no RFs, 11 of 230 = 5%; one RF, 31 of 278 = 11%; two RFs, 36 of 202 = 18%; three RFs, 41 of 110 = 37%; four RFs, 19 of 42 = 45%; and five RFs, 5 of 10 = 50% (P < 0.001). The odds ratio (OR) for conversion to type 2 diabetes for each additional RF was 2.1 (95% CI 1.78-2.46) after adjusting for age, sex, ethnicity, and center. After further adjustment for insulin resistance, determined by the frequently sampled intravenous glucose tolerance test and waist circumference, each additional CVD RF increased the risk of type 2 diabetes significantly (OR 1.81, 95% CI 1.49-2.20). CONCLUSIONS: Individuals with multiple CVD RFs are at increased risk of type 2 diabetes, which is only partially mediated by insulin resistance or central adiposity. This information should be useful for identifying high-risk patients for developing diabetes through RF assessments ( view less ) View Full Abstract View Article Details   Related Articles Prediction of type 2 diabetes using simple measures of insulin resistance: combined results from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study.[erratum appears in Diabetes. 2003 May;52(5):1306] 2003 Hanley, A. J., Williams, K., Gonzalez, C., D'Agostino, R. B. J., Wagenknecht, L. E., Stern, M. P., Haffner, S. M., San, AntonioHeartStudy, Mexico, CityDiabetesStudy, and Insulin, ResistanceAtherosclerosisStudy To determine and formally compare the ability of simple indexes of insulin resistance (IR) to predict type 2 diabetes, we used combined prospective data from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study, which include well-characteriz... ( view more )ed cohorts of non-Hispanic white, African-American, Hispanic American, and Mexican subjects with 5-8 years of follow-up. Poisson regression was used to assess the ability of each candidate index to predict incident diabetes at the follow-up examination (343 of 3,574 subjects developed diabetes). The areas under the receiver operator characteristic (AROC) curves for each index were calculated and statistically compared. In pooled analysis, Gutt et al.'s insulin sensitivity index at 0 and 120 min (ISI(0,120)) displayed the largest AROC (78.5%). This index was significantly more predictive (P < 0.0001) than a large group of indexes (including those by Belfiore, Avignon, Katz, and Stumvoll) that had AROC curves between 66 and 74%. These findings were essentially similar both after adjustment for covariates and when analyses were conducted separately by glucose tolerance status and ethnicity/study subgroups. In conclusion, we found substantial differences between published IR indexes in the prediction of diabetes, with ISI(0,120) consistently showing the strongest prediction. This index may reflect other aspects of diabetes pathogenesis in addition to IR, which might explain its strong predictive abilities despite its moderate correlation with direct measures of IR ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Intact proinsulin, des 31,32 proinsulin, and specific insulin concentrations among nondiabetic and diabetic subjects in populations at varying risk of type 2 diabetes 1998 Nagi, D. K., Knowler, W. C., Mohamed-Ali, V., Bennett, P. H., and Yudkin, J. S. OBJECTIVE: To examine hyperinsulinemia, insulin secretion, and beta-cell function in Pima Indians, South Asians, and whites, populations at varying risk of diabetes. RESEARCH DESIGN AND METHODS: We investigated 136 Pima Indian, 98 Asian, and 80 white nondiabetic and 172 Pima Indian, 40 Asian, and 4... ( view more )9 white diabetic subjects. Highly specific assays for insulin, intact proinsulin, and des 31,32 proinsulin were used. Insulin secretion was assessed using ratio of increment (0 to 30 min) in insulin to glucose concentrations during an oral glucose tolerance test (OGTT). RESULTS: Nondiabetic Pima Indians were significantly more obese than Asians and whites. Pima Indian subjects had significantly higher (P < 0.01) fasting insulin concentrations (median 109 pmol/l, range 40-250) than Asian (37 pmol/l, range 17-91) and white (30 pmol/l, range 10-82) subjects. These differences remained significant when controlled for obesity. Nondiabetic Pima Indians also had higher fasting C-peptide concentrations and higher early insulin secretion during an OGTT. Fasting concentrations of intact proinsulin and des 31,32 proinsulin were also significantly higher in Pima Indians (P < 0.01). However, the proportion of proinsulin-like molecules was significantly lower (P < 0.01) in Pima Indians (median 7.9% vs. 12.7% for South Asians and 12.2% for whites). Subjects with diabetes from the three ethnic groups showed significantly higher fasting insulin concentrations but lower 30-min insulin and lower ratios of increment (0-30 min) in insulin to glucose concentrations than did nondiabetic subjects. The proportion of proinsulin-like molecules was not significantly different in diabetic subjects from the three ethnic groups. CONCLUSIONS: These specific assays for insulin indicate that after adjusting for obesity nondiabetic Pima Indians are truly hyperinsulinemic, which is consistent with their insulin resistance as measured by other methods. Hyperinsulinemia in this population with a high risk of diabetes is likely to be due to enhanced insulin secretion. Furthermore, in Pima Indians, the predominant beta-cell secretory product is insulin and not its precursors. We conclude that the differences in the risk of diabetes among these three groups are not due to differences in insulin secretion or insulin processing. Subjects with type 2 diabetes have defective early insulin secretion during OGTTs but show fasting hyperinsulinemia even when specific assays for insulin are used ( view less ) View Full Abstract View Article Details   Related Articles Sex differences in the association between proinsulin and intact insulin with coronary heart disease in nondiabetic older adults: the Rancho Bernardo Study.[see comment] 2002 Oh, J. Y., Barrett-Connor, E., and Wedick, N. M. BACKGROUND: Insulin or insulin resistance is considered a coronary heart disease (CHD) risk factor, but proinsulin may have a stronger association with CHD than insulin. The role of sex differences in this association is unclear. We examined the cross-sectional association of proinsulin and insulin... ( view more ) with CHD in older men and women without diabetes. METHODS AND RESULTS: A cross-sectional study of community-dwelling men (n=554) and women (n=902), 50 to 97 years of age, without diabetes by history or oral glucose tolerance test, was done between 1992 and 1996; plasma levels of intact insulin, proinsulin, and C-peptide were measured by radioimmunoassay. Based on questionnaire, medical history, or ECG abnormalities, 25% of men (n=136) and 24% of women (n=214) had prevalent CHD. All insulin variables were positively correlated with CHD risk factors. Compared with those without CHD, men and women with CHD had significantly higher levels of proinsulin. Women but not men with CHD also had higher levels of C-peptide and fasting and postchallenge insulin. Only proinsulin was significantly and independently associated with prevalent CHD in both men (OR=2.41, 1.42 to 4.11) and women (OR=1.80, 1.22 to 2.64) (adjusted for age, body mass index, systolic blood pressure, and HDL cholesterol). Similar analyses for fasting and postchallenge intact insulin and for C-peptide showed that among these three variables, only postchallenge insulin was significantly associated with CHD, and only in women. CONCLUSIONS: In older nondiabetic men and women, proinsulin was more strongly and consistently associated with CHD than was intact insulin ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Effect of metformin on intact proinsulin and des 31,32 proinsulin concentrations in subjects with non-insulin-dependent (type 2) diabetes mellitus 1996 Nagi, D. K., Ali, V. M., and Yudkin, J. S. We have investigated the effects of metformin treatment on concentrations of proinsulin-like molecules in subjects with Type 2 (non-insulin-dependent) diabetes mellitus. Metformin was given for 12 weeks in an increasing dose up to 850 mg three times daily in a double-blind placebo-controlled cross-... ( view more )over design to 27 subjects (age 53.0 +/- 9.9 years; 19 male, 8 female). Concentrations of insulin and proinsulin-like molecules were measured by highly specific enzymoimmunometric assays. The end of metformin treatment was compared with end of placebo treatment. Metformin lowered fasting plasma glucose concentrations (at 12 weeks, metformin: 8.0 +/- 2.5 vs placebo: 12.0 +/- 2.3 mmol l-1, p r2 0.001;). Concentrations of intact (median change -2.9 (range -28.4 to +2.5 pmol l-1), p = 0.02) and des 31,32 proinsulin (median change -1.6 (range -14.1 to +5.4 pmol l-1), p = 0.07) and percentage of proinsulin-like molecules were reduced by metformin treatment (median change -6% (range -16% to +6%), p = 0.02). Changes in the ratio of proinsulin-like molecules were significantly related with those in fasting plasma glucose (r1 = 0.69, p < 0.001). Changes in concentrations of intact and des 31,32 proinsulin on metformin were not related to changes in body mass index or fasting glucose concentration or changes in concentrations of total triglyceride, cholesterol, and plasminogen activator inhibitor-1. Therefore, metformin treatment in subjects with Type 2 diabetes mellitus significantly reduced concentrations of proinsulin-like molecules over a 12-week period. However, these changes were not related to changes in cardiovascular risk factors seen during metformin treatment. We conclude that short-term effects of metformin treatment on proinsulin-like molecules are similar to those previously observed with dietary treatment in subjects with Type 2 diabetes but opposite to those of sulphonylurea treatment. The effect of long-term treatment with metformin on proinsulin-like molecules needs to be assessed ( view less ) View Full Abstract View Article Details   Related Articles Total immunoreactive proinsulin, immunoreactive insulin and specific insulin in relation to conversion to NIDDM: the Mexico City Diabetes Study 1997 Haffner, S. M., Gonzalez, C., Mykkanen, L., and Stern, M. Although insulin resistance and decreased insulin secretion are characteristic of established non-insulin-dependent diabetes mellitus (NIDDM), which of these metabolic abnormalities is the primary determinant of NIDDM is still controversial. A disproportionate increase in the proinsulin to insulin ... ( view more )ratio has been proposed as a marker of compromised insulin secretion. We examined the association of fasting immunoreactive insulin (which cross-reacts with proinsulin), specific insulin (which does not cross-react with proinsulin), total immunoreactive proinsulin (or insulin precursors), and the fasting proinsulin/specific insulin ratio to the risk of developing NIDDM in the 3.25-year follow-up of the Mexico City Diabetes Study. These measurements were made in 85 subjects who subsequently converted to NIDDM (prediabetic subjects) and in 85 age and gender matched subjects who remained non-diabetic at follow-up (control subjects). Immunoreactive insulin, proinsulin and the proinsulin/specific insulin ratio were significantly higher in prediabetic than in control subjects. However, the relation between specific insulin and the development of NIDDM was weaker than for proinsulin or immunoreactive insulin. After further adjustment for obesity, body fat distribution and glucose tolerance status, proinsulin and the proinsulin/specific insulin ratio, but not specific or immunoreactive insulin, predicted conversion to NIDDM. A high proinsulin/specific insulin ratio predicted conversion to NIDDM both in subjects with normal and those with impaired glucose tolerance at baseline. We conclude that in prediabetic subjects increased proinsulin, a marker of islet cell distress or compromised insulin secretion, is associated with rapid conversion (within 3.25 years) to NIDDM even in obese populations ( view less ) View Full Abstract View Article Details   Related Articles Significant association of insulin and proinsulin with clustering of cardiovascular risk factors 1-5-1907 Jia, E. Z., Yang, Z. J., Chen, S. W., Qi, G. Y., You, C. F., Ma, J. F., Zhang, J. X., Wang, Z. Z., Qian, W. C., Li, X. L., Wang, H. Y., and Ma, W. Z. AIM: To investigate the association between true insulin and proinsulin and clustering of cardiovascular risk factors. METHODS: Based on the random stratified sampling principles, 1196 Chinese people (533 males and 663 females, aged 35-59 years with an average age of 46.69 years) were recruited. Bi... ( view more )otin-avidin based double monoclonal antibody ELISA method was used to detect the true insulin and proinsulin, and a risk factor score was set to evaluate individuals according to the number of risk factors. RESULTS: The median (quartile range) of true insulin and proinsulin was 4.91 mIu/L (3.01-7.09 mIu/L) and 3.49 pmol/L (2.14-5.68 pmol/L) respectively, and the true insulin level of female subjects was significantly higher than that of male subjects (P = 0.000), but the level of proinsulin displayed no significant difference between males and females (P = 0.566). The results of covariate ANOVA after age and sex were controlled showed that subjects with any of the risk factors had a significantly higher true insulin level (P = 0.002 for hypercholesterolemia, P = 0.021 for high low-density lipoprotein cholesterol, P = 0.003 for low high-density lipoprotein cholesterol, and P = 0.000 for other risk factors) and proinsulin level (P = 0.001 for low high-density lipoprotein cholesterol, and P = 0.000 for other risk factors) than those with no risk factors. Furthermore, subjects with higher risk factor scores had a higher true insulin and proinsulin level than those with lower risk factor scores (P = 0.000). The multiple linear regression models showed that true insulin and proinsulin were significantly related to cardiovascular risk factor scores respectively (P = 0.000). CONCLUSION: True insulin and proinsulin are significantly associated with the clustering of cardiovascular risk factors ( view less ) View Full Abstract View Article Details   Related Articles Are insulin and proinsulin independent risk markers for premature coronary artery disease ? 1996 Katz, R. J., Ratner, R. E., Cohen, R. M., Eisenhower, E., and Verme, D. Controversy persists about whether hyperinsulinemia and hyperproinsulinemia are independent risk markers for coronary atherosclerosis. A common limitation of most previous studies has been imprecise categorization of disease status in normal and coronary artery disease (CAD) groups. We assessed the... ( view more ) relationship of pancreatic beta-cell secretory products and premature CAD in a case-control study of 134 nondiabetic subjects, aged < or = 55 years old, carefully defined for CAD status by catheterization and/or thallium stress studies. Case patients comprised 66 patients with premature CAD, and control subjects (non-CAD group) included 68 patients without CAD but with traditional CAD risk factors and chest pain and/or abnormal electrocardiograms but normal catheterization and/or thallium stress studies. In addition to the CAD and non-CAD group comparison, both groups were compared with a reference group of 27 mixed lean and obese control volunteers. All CAD and non-CAD patients had a 3-h 75-g oral glucose tolerance test with measurement of fasting and post-glucose load immunoreactive insulin (IRI), specific insulin (INS), proinsulin-like material (PI), and C-peptide. Increased fasting insulin and fasting proinsulin levels both were statistically significantly associated with higher odds of being in either the premature CAD and the non-CAD groups when compared with the reference group in a polychotomous logistic regression model (odds ratio of at least 1.20 for a 20% increase in each beta-cell secretory product in both comparisons, P < 0.05). However, increased pancreatic beta-cell secretory hormone levels did not show a statistically significant relative risk for being in the premature CAD group when compared with the non-CAD group. After adjustment for BMI, all statistically significant associations disappeared for IRI, INS, and PI when the odds favoring being in the CAD and non-CAD groups were compared versus the reference group. Furthermore, the odds of being in the premature CAD and non-CAD groups when compared with the reference group were not significantly associated to the ratio of PI to insulin and C-peptide. Thus, although there is a statistically significant association between the odds of having premature CAD with elevated insulin and proinsulin levels compared with the reference group, these findings are equally common in subjects with traditional CAD risk factors without detectable CAD. Furthermore, the association of higher insulin and proinsulin levels with the likelihood of a patient having or not having CAD disappears after adjustment for BMI, suggesting that insulin and proinsulin are not independent risk markers but are primarily dependent on obesity ( view less ) View Full Abstract View Article Details   Related Articles Proinsulin levels predict the development of non-insulin-dependent diabetes mellitus (NIDDM) in Japanese-American men 1996 Kahn, S. E., Leonetti, D. L., Prigeon, R. L., Boyko, E. J., Bergstom, R. W., and Fujimoto, W. Y. Disproportionate hyperproinsulinaemia is a manifestation of the beta-cell dysfunction observed in NIDDM. However, it is unclear when this abnormality develops and whether it predicts the development of the disease. To examine whether changes in proinsulin levels predict the development of NIDDM, ba... ( view more )seline measurements of proinsulin and immunoreactive insulin levels were made in 87 second-generation Japanese-American men, a population at high risk for the subsequent development of NIDDM. Subjects were categorized at baseline using WHO criteria as having normal glucose tolerance (NGT; n = 49) or impaired glucose tolerance (IGT; n = 38). After a 5-year follow-up period, subjects were recategorized as having NGT, IGT or NIDDM using the same criteria. During follow-up, 16 subjects developed NIDDM while 71 were NGT or IGT. At baseline, individuals who subsequently developed NIDDM were more obese as measured by intra-abdominal fat area on computed tomography (p = 0.046), had higher fasting glucose (p = 0.0042), 2-h glucose (p = 0.0002), fasting C-peptide (p = 0.0011), fasting proinsulin levels (p = 0.0033), and had disproportionate hyperproinsulinaemia (p = 0.056) when compared to those who remained NGT or IGT after 5 years of follow-up. These findings suggest that alterations in proinsulin levels may also predict the subsequent development of NIDDM ( view less ) View Full Abstract View Article Details   Related Articles Fasting proinsulin and 2-h post-load glucose levels predict the conversion to NIDDM in subjects with impaired glucose tolerance: the Hoorn Study 1996 Nijpels, G., Popp-Snijders, C., Kostense, P. J., Bouter, L. M., and Heine, R. J. The aims of the present study were to observe the natural history of impaired glucose tolerance and to identify predictors for development of non-insulin-dependent diabetes mellitus (NIDDM). A survey of glucose tolerance was conducted in subjects aged 50-74 years, randomly selected from the registr... ( view more )y of the middle-sized town of Hoorn in the Netherlands. Based on the mean values of two oral glucose tolerance tests subjects were classified in categories of glucose tolerance according to the World Health Organization criteria. All subjects with impaired glucose tolerance (n = 224) were invited to participate in the present study, in which 70% (n = 158) were subsequently enrolled. During follow-up subjects underwent a repeated paired oral glucose tolerance test. The mean follow-up time was 24 months (range 12-36 months). The cumulative incidence of NIDDM was 28.5% (95% confidence interval 15-42%). Age, sex, and anthropometric and metabolic characteristics at baseline were analysed simultaneously as potential predictors of conversion to NIDDM using multiple logistic regression. The initial 2-h post-load plasma glucose levels and the fasting proinsulin levels were significantly (p < 0.05) related to the incidence of NIDDM. Anthropometric characteristics, the 2-h post-load specific insulin levels and the fasting proinsulin/fasting insulin ratio were not related to the incidence of NIDDM. These results suggest that beta-cell dysfunction rather than insulin resistance plays the most important role in the future development of diabetes in a high-risk Caucasian population ( view less ) View Full Abstract View Article Details   Related Articles A higher proinsulin response to glucose loading predicts deteriorating fasting plasma glucose and worsening to diabetes in subjects with impaired glucose tolerance.[erratum appears in Diabet Med 1996 Aug;13(8):775] 1996 Inoue, I., Takahashi, K., Katayama, S., Harada, Y., Negishi, K., Ishii, J., Shibazaki, S., Nagai, M., and Kawazu, S. To evaluate the clinical significance of proinsulin determination, we measured glucose, insulin, C-peptide and proinsulin during 75-g oral glucose loading in 59 patients. In a 2.5-year follow-up study of 37 subjects with impaired glucose tolerance (IGT) at the initial test, 11 patients changed from... ( view more ) IGT to a normal state and 5 patients showed worsening to overt Type 2 diabetes with elevation of fasting plasma glucose; 21 patients remained unchanged. Although our data showed that both fasting (IGT: p = 0.4523) and 120-min plasma glucose (IGT: p = 0.8168) values at the initial test were not significantly correlated with increased fasting plasma glucose levels in a 2.5-year follow-up study, subjects with a higher 120-min proinsulin response to glucose during the initial OGTT showed a significant correlation (IGT: p < 0.0001) with increased fasting plasma glucose levels after follow-up period and developed Type 2 diabetes. The present findings suggest that the proinsulin response to glucose loading might be a useful indicator for predicting worsening to diabetes in subjects with impaired glucose tolerance ( view less ) View Full Abstract View Article Details   Related Articles Cross-sectional and prospective associations between proinsulin and cardiovascular disease risk factors in a population experiencing rapid cultural transition.[erratum appears in Diabetes Care 2001 Oct;24(10):1851] 2001 Hanley, A. J., McKeown-Eyssen, G., Harris, S. B., Hegele, R. A., Wolever, T. M., Kwan, J., Connelly, P. W., and Zinman, B. OBJECTIVE: To examine cross-sectional and prospective associations between proinsulin and cardiovascular disease risk factors using data from a population-based study of type 2 diabetes among Native Canadians. RESEARCH DESIGN AND METHODS: Between 1993 and 1995, 72% of eligible members of a Native C... ( view more )anadian community participated in a baseline diabetes prevalence survey. Fasting samples were collected for glucose, C-peptide, proinsulin, lipids, and apolipoproteins. A 75-g oral glucose tolerance test was administered, and a second sample for glucose was drawn after 120 min. Blood pressure and waist circumference were determined. In the present study, subjects with normal glucose tolerance (NGT) (n = 505) and impaired glucose tolerance (IGT) (n = 74) were included in cross-sectional analyses. In 1998, 95 individuals who had IGT or NGT at baseline with an elevated 2-h glucose concentration (> or = 7.0 mmol/l) participated in a follow-up evaluation using the protocol used at baseline. Cross-sectional and prospective associations between proinsulin and cardiovascular risk factors were assessed using correlation and multiple linear regression analyses. RESULTS: After adjustment for covariates including age, sex, C-peptide, waist circumference, and glucose tolerance status, fasting proinsulin concentration was significantly associated with concurrently measured lipid and apolipoprotein concentrations (triglycerides: r = 0.18, P < 0.0001; total cholesterol: r = 0.10, P = 0.02; LDL cholesterol: r = 0.11, P = 0.01; HDL cholesterol: r = -0.16, P = 0.0002; apolipoprotein (apo) B: r = 0.17, P < 0.0001; apoAI: r = -0.11, P = 0.008). In the adjusted prospective analysis, baseline triglycerides, HDL cholesterol, and apoB were associated with changes over time in proinsulin (r = 0.23, P = 0.04; r = -0.30, P = 0.01; r = 0.23, P = 0.04; respectively). CONCLUSIONS: These results confirm previously reported cross-sectional associations between proinsulin and lipid concentrations. In addition, an unexpected association between baseline lipids and proinsulin change was documented ( view less ) View Full Abstract View Article Details   Related Articles Evaluation of a scoring scheme, including proinsulin and the apolipoprotein B/apolipoprotein A1 ratio, for the risk of acute coronary events in middle-aged men: Uppsala Longitudinal Study of Adult Men (ULSAM) 2004 Dunder, K., Lind, L., Zethelius, B., Berglund, L., and Lithell, H. BACKGROUND: In recent years, the importance of circulating levels of proinsulin and apolipoproteins as risk factors for myocardial infarction (MI) has been highlighted. The aims of the current study were to investigate whether introduction of these new markers of coronary risk could improve the per... ( view more )formance of a risk prediction score and to compare this new score with traditional scoring schemes, such as the Framingham Study and the Prospective Cardiovascular Munster (PROCAM) Study schemes. METHODS: From 1970 to 1973 all 50-year-old men in Uppsala, Sweden, were invited to participate in a health survey aimed at identifying risk factors for cardiovascular disease (the Uppsala Longitudinal Study of Adult Men [ULSAM] cohort). The current study investigated metabolic characteristics at baseline and the incidence of fatal and nonfatal MI (n = 251) during 28.7 years of follow-up in 1108 men who were free of coronary heart disease at baseline. RESULTS: The risk prediction score was derived from one half of the population sample from the ULSAM cohort and included systolic blood pressure, smoking, family history of MI, serum proinsulin, and the ratio between apolipoprotein B and apolipoprotein A1.The score was highly predictive for future MI (hazard ratio, 1.77 for a 1 SD increase; 95% CI, 1.49 to 2.10, P <.0001) in the other half of the population that was not used for generating the score. The ULSAM score performed slightly better than the Framingham and PROCAM scores (evaluated as areas under the receiver operating curves; Framingham, 61%; PROCAM, 63%; ULSAM, 66%; P =.08). CONCLUSIONS: A risk prediction score for MI including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1 was developed in middle-aged men. This score was highly predictive for future fatal and nonfatal MI and proved to be at least as good as the Framingham and the PROCAM scores, being based on traditional risk factors ( view less ) View Full Abstract View Article Details   Related Articles Evaluation of a scoring scheme, including proinsulin and the apolipoprotein B/apolipoprotein A1 ratio, for the risk of acute coronary events in middle-aged men: Uppsala Longitudinal Study of Adult Men (ULSAM) 2004 Dunder, K., Lind, L., Zethelius, B., Berglund, L., and Lithell, H. Background In recent years, the importance of circulating levels of proinsulin and apolipoproteins as risk factors for myocardial infarction (MI) has been highlighted. The aims of the current study were to investigate whether introduction of these new markers of coronary risk could improve the perf... ( view more )ormance of a risk prediction score and to compare this new score with traditional scoring schemes, such as the Framingham Study and the Prospective Cardiovascular Munster (PROCAM) Study schemes. Methods From 1970 to 1973 all 50-year-old men in Uppsala, Sweden, were invited to participate in a health survey aimed at identifying risk factors for cardiovascular disease (the Uppsala Longitudinal Study of Adult Men [ULSAM] cohort). The current study investigated metabolic characteristics at baseline and the incidence of fatal and nonfatal MI (n = 251) during 28.7 years of follow-up in 1108 men who were free of coronary heart disease at baseline. Results The risk prediction score was derived from one half of the population sample from the ULSAM cohort and included systolic blood pressure, smoking, family history of MI, serum proinsulin, and the ratio between apolipoprotein B and apolipoprotein A1.The score was highly predictive for future MI (hazard ratio, 1.77 for a 1 SD increase; 95% CI, 1.49 to 2.10, P < .0001) in the other half of the population that was not used for generating the score. The ULSAM score performed slightly better than the Framingham and PROCAM scores (evaluated as areas under the receiver operating curves; Framingham, 61%; PROCAM, 63%; ULSAM, 66%; P = .08). Conclusions A risk prediction score for MI including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1 was developed in middle-aged men. This score was highly predictive for future fatal and nonfatal MI and proved to be at least as good as the Framingham and the PROCAM scores, being based on traditional risk factors ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Enhancement of liver size by stimulation of intact rat liver with exogenous hepatotrophic factors. 1995 Jul-Aug O M Parra,R A de Sousa e Silva,J R da Silva,F J Hernandez-Blasquez,L Peduto,W A Saad,W A Saad Junior In mammals, liver size is related to animal body weight at the 2.5 to 3% proportion, a ratio mediated by the afflux of hepatotrophic factors. Formulas capable of modifying this ratio have been developed in previous studies on the rat, with enhancement of liver size brought about by intraperitoneal ... ( view more )(portal) infusion of exogenous factors such as glucose, amino acids, insulin, glucagon, vitamins, electrolytes, and triiodothyronine. However, the efficacy of these formulations was accompanied by increased animal mortality (PARRA et al.). The present study, which was carried out with small methodological modifications on a larger number of rats using daily intraperitoneal injections of a solution of exogenous hepatotrophic factors (40 ml/kg) for seven days, confirms the previous findings, with a 114.16 +/- 7.90% enhancement of liver size beyond the expected value for the body weight of the animal. However, the problem of animal mortality was not fully resolved. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles [Surgical strategy for transposition of the great arteries with intact ventricular septum after the neonatal period] Jul 2005 Bayard Gontijo Filho,Fernando A Fantini,Cristiane Martins,Roberto Max Lopes,Roberto de S Thiago Pereira,Sonia Maria Rabelo,Eliana Heyden,Erika Vrandecic,Mario O Vrandecic OBJECTIVE: To assess the surgical results in patients with transposition of the great arteries and intact ventricular septum undergoing surgery after the neonatal period. METHODS: From January 1998 to March 2004, 121 children with transposition of the great arteries with intact ventricular septum w... ( view more )ere treated, 29 (24%) of whom after the neonatal period. Selection for surgical treatment was based on echocardiographic assessment by use of the calculation of left ventricular mass and configuration of the ventricular septum. Of the 29 children, 12 were selected for primary anatomic correction, 12 for 2-stage correction after surgical preparation of the left ventricle, and 5 underwent atrial correction. RESULTS: In the group undergoing primary anatomic correction, one (8.3%) patient died at the hospital due to sepsis. In the group undergoing 2-stage correction, 5 patients underwent slow preparation with correction 3-6 months after the first stage, 4 of whom died after the first stage. This fact caused a change in our protocol, with adoption of the rapid preparation technique in the other 7 patients, of whom all achieved the second stage. Of the 8 children undergoing the second stage, one died at the hospital and another died later. Late clinical evolution of the children in both groups is excellent. CONCLUSION: The echocardiographic selection allowed a safe choice of the best surgical approach for patients with transposition of the great arteries and intact ventricular septum after the neonatal period. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles [Effect of hypothyroidism on the solid form of Ehrlich tumor in intact or castrated adult female mice] Dec 2004 Alessandra Estrêla da Silva,Rogéria Serakides,Enio Ferreira,Jáder R Cappi Moraes,Natália de Melo Ocarino,Geovanni Dantas Cassali The effect of hypothyroidism on the solid form of the Ehrlich tumor in intact or castrated adult female mice was studied. Hypothyroidism was induced by treatment with propylthiouracil (PTU). Forty mice were divided into four groups: castrated hypothyroid, intact hypothyroid, castrated euthyroid, an... ( view more )d intact euthyroid. The mice were inoculated with suspension cells into the left footpad. The tumor growth curve was determined by measuring the inoculated footpad during 12 days. At the end of the experimental period the mice were sacrificed. Hypothyroidism was associated with a reduction in size of the tumor only in the castrated animals. Although the neoplastic growth was lower, mean nuclear diameter, number of nucleolar organizer regions (NORs), and area of mitosis were higher. In conclusion, hypothyroidism resulted in a delayed growth of the tumor, but it did not affect the malignant features of the neoplastic cells. In addition, the isolated effect of castration caused only mild alterations, whereas hypothyroidism associated with castration resulted in a more prominent delay in the growth rate of the Ehrlich tumor. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Effects of a restricted diet on the submaxillary gland of intact and castrated male rats. Dec 1989 A Goldraij,M L Rins de David,P Fernandez Delgado Effects of diet restriction (50% of normal) during 4 weeks were studied in intact (controls) and castrated rats. A restricted diet led to cessation of animal growth. No differences were observed between controls and castrated rats. However, underfeeding produced a reduction of testicular weight in ... ( view more )intact rats. Histochemical observations showed a reduction of tryptophan (a marker of the presence of testosterone-dependent protein) in the submaxillary gland from animals fed a restricted-diet. In animals fed a normal diet, castration reduced significantly the gland weight, as well as the diameter of tubules and acini. When animals fed a restricted-diet are compared, no significant differences were found in the diameter of tubules and acini or in the weight of submaxillary glands. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles [Pulmonary atresia with an intact interventricular septum and Ebstein's anomaly of the tricuspid valve] 1989 Mar-Apr D Guzzo,C Castellano,L Muñoz-Castellanos,J de Rubens,J Calderón,F Attié Patients with pulmonary atresia and intact ventricular septum have a poor prognosis with or without conventional surgical treatment. The best results of surgical treatment are obtained in those cases with a mild underdeveloped right ventricle and minor sinusoidal communication in the absence of imp... ( view more )ortant dysfunction of the tricuspid valve. We present five cases of pulmonary atresia with intact ventricular septum associated with dysfunction of the tricuspid valve. On the basis of radiographic, electrocardiographic and hemodynamic findings, this group of patients could not be distinguished from others without dysplasia of the tricuspid valve. Echocardiographic and angiocardiographic studies are mandatory in the differential diagnosis. A combination of systemic-pulmonary artery anastomosis associated with pulmonary valvotomy, when possible, and reconstruction of the right ventricular outflow tract are indicated for surgical solution of these malformations. However, tricuspid valve replacement is indicated in some cases. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Biomechanical effects of unipedicular vertebroplasty on intact vertebrae 7-3-1915 Higgins, K. B., Harten, R. D., Langrana, N. A., and Reiter, M. F. STUDY DESIGN: To assess the biomechanical effects of unipedicular vertebroplasty on nonfractured vertebrae. OBJECTIVES: To evaluate the potential benefits of vertebroplasty as a preventative treatment. To evaluate the effects of cement volume and bone mineral density on the mechanics of augmented i... ( view more )ntact vertebral bodies. SUMMARY OF BACKGROUND DATA: Many studies have been undertaken to examine the effects of augmentation procedures such as vertebroplasty or kyphoplasty on fractured vertebral bodies. However, the role of such procedures as a prophylactic or interventional tool has not been well studied. This approach may be of clinical interest due to the high occurrence of secondary compression fractures and potentially altered biomechanics following an isolated vertebroplasty procedure. METHODS: Nonfractured osteoporotic vertebrae were measured to calculate volume and DEXA scanned to obtain bone mineral density information. Randomly selected specimens were injected with 10% and 20% bone cement by volume or left unfilled to serve as controls. After radiographs and noted cement leakage, specimens were subjected to destructive compression testing. RESULTS: It was found that the injection of 20% bone cement by volume in the lumbar levels resulted in a statistically significant 36% strength increase as compared with the unfilled controls regardless of density levels. However, in the upper thoracic vertebrae there was no significant difference between the strengths of the three groups. Additionally, injection of 20% bone cement frequently resulted in extravasation through vascular channels or into the spinal canal. CONCLUSIONS: The introduction of 20% bone cement by volume results in a significant increase in the compressive strength of intact lumbar vertebrae, however upper thoracic vertebrae do not demonstrate a similar strength improvement. There was no difference in the stiffness of the vertebrae injected with cement regardless of location. Bone mineral density (BMD) may play a role in the magnitude of the strength increase, with lower BMD specimens realizing a relatively greater strength improvement. Cement leakage was frequently noted with 20% cement injection, especially in the specimens with higher BMD. The location of the cement did not appear to have an effect on the loading behavior of the bone but should be controlled to minimize the chance of cement escaping into the spinal canal ( view less ) View Full Abstract View Article Details   Related Articles [Echocardiographic diagnosis of pulmonary atresia with intact interventricular septum and associated Ebstein anomaly] 1987 Sep-Oct C Castellano,M Pérez de Juan,J Vargas Barrón,A Buendía,L Muñóz Castellanos,F Attié Pulmonary atresia with intact ventricular septum is an uncommon congenital cardiac anomaly which very often present varying degrees of downward displacement and dysplasia of the tricuspid valve. We describe a case of pulmonary atresia and intact ventricular septum associated with Ebstein's malforma... ( view more )tion of the tricuspid valve first diagnosed with echocardiography and confirmed by angiocardiography and anatomic studies. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles [Blood profile of hypothyroid castrated or intact adult female rats] Apr 2004 Mardelene G Gomes,Rogéria Serakides,Vera Alvarenga Nunes,Cristiana M da Silva,Rubens A Carneiro,Natália de M Ocarino The relationship between thyroid-gonads on the blood profile was investigated in adult Wistar female rats. These animals were either castrated or intact and were kept under hypothyroidism, induced by daily administration of propylthiouracil (PTU) during 120 days. Two groups (castrated and intact) w... ( view more )ere kept in an euthyroid condition and used as controls. It was collected plasma for free T4 dosage and blood for hematological analysis. The significant low values of free T4 in the treated rats confirmed their hypothyroid state. The hypothyroidism caused anemia in the rats with functional gonads. The castration reverted the effects of thyroxine deficit in the erythrogram. Both the hypothyroidism and the hypogonadism showed just a discret effect on the leucogram. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Page 1 of 1000 1 2 3 4 > Last >> (25000 articles found)

      
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